Ch. 25 – Metabolism and Energetics

• Slides marked “MP” in the upper corner indicate information that is important for understanding and completing the Metabolic Pathways Exam and ARE NOT fair game for Lecture Exam 2.

• Slides marked “KNOW” in the upper corner indicate information that IS fair game for Lecture Exam 2.

• We will not be covering Ch. 25 in its entirety, but we will be pulling bits and pieces of info from it – Read the parts of this chapter that help you understand

the material on the lecture slides, but be assured that material that we don’t cover in lecture will not be fair game for the exams (Metabolic Pathways or Lecture Exam 2)

Metabolism• = the sum of all chemical reactions occurring in the body

– Chemical reactions convert energy from one form to another• Chemical bonds are broken, atoms are rearranged, and new bonds are

formed– Electrons are transferred, rearranged, and/or shared

• Anabolic reactions:– Require an input of energy (i.e., they are endergonic)– Synthesize complex organic molecules from simpler ones

• Catabolic reactions:– Release energy (i.e., they are exergonic)– Break down complex organic molecules into simpler ones– E.g. glycolysis, the citric acid (tricarboxylic acid or TCA) cycle, and the

electron transport system (ETS)• Both types of reactions require enzymes• Energy derived from catabolism is used to drive anabolism• The efficiency of ATP (energy) generation = ~ 40%

– I.e., ~ 60% is lost as heat• But this efficiency is actually much higher than the efficiency of many

human-made machines!

KNOW

Fig. 25-1, p. 918

KNOW An overview of cellular metabolism

Electrons and chemical energy• 1. Electrons (e-) are the “glue” that hold atoms

together in covalent bonds, and they store chemical energy – E.g., the bonds between carbons in organic compounds

such as carbohydrates, lipids, and proteins– E.g., the “high-energy bonds” that involve phosphate

groups in molecules such as ATP or GTP– Breaking these bonds releases chemical energy

• 2. So-called “high-energy electrons” can be passed between molecules in oxidation-reduction (redox) reactions, releasing chemical energy– Oxidation is the loss of electrons from a molecule (which is

called the donor molecule)– Reduction is the gain of electrons by a molecule (which is

called the acceptor molecule)• Note that the acceptor molecule’s oxidation state (≈ charge) is

“reduced” (i.e., it becomes more negative) by the addition of negatively charged electrons

MP

Electron/hydrogen carriers• Biological redox reactions often involve the transfer

of 2 hydrogen (H) atoms (and their electrons) in the form of a proton (H+) and a hydride ion (H- = H+ + 2 e-)

• 2 important coenzymes that carry the electrons and hydrogens from one redox reaction to another are:– 1. NAD+ (nicotinamide adenine dinucleotide)

• NAD+ (oxidized) + 2 H•• ↔ NADH•• (reduced) + H+

– 2. FAD (flavin adenine dinucleotide)• FAD (oxidized) + 2 H•• ↔ FADH2•• (reduced)

Note: the symbol •• represents the 2 electrons that are being transferred

– So both of the reduced coenzymes are carrying a pair of “high-energy electrons”

MP

Some methods of ATP generationMP

• 1. Substrate-level phosphorylation:– An inorganic phosphate is transferred from a metabolic

intermediate molecule (substrate) to ADP, forming ATP

• 2. Oxidative phosphorylation:– A. Electrons move from high energy carriers (like NAD+)

to progressively lower energy carriers in the electron transport system (ETS) of the mitochondrion • The electrons ultimately wind up on the terminal acceptor

molecule, oxygen

– B. The energy released as the electrons move along the ETS is used to produce a H+ gradient across the mitochondrial inner membrane

– C. When H+ diffuses down its concentration gradient through a membrane protein called ATP synthase, the energy released is used to phosphorylate ADP into ATP

Fig. 25-2, p. 919

An overview of metabolic pathwaysMP

Glucose catabolism and oxidation• The overall formula:

C6H12O6 + 6 O2 + 36 ADP + 36 Pi → 6 CO2 + 6 H2O + 36 ATP + heat

• It occurs in 3 stages:– 1. Glycolysis = the breakdown of glucose to pyruvate

(pyruvic acid)• It’s an example of anaerobic cellular metabolism; i.e., O2 is not

required• It takes place in the cytoplasm

– 2. The citric acid cycle = tricarboxylic acid (TCA) cycle = Krebs cycle • It’s the first part of aerobic cellular metabolism (cellular respiration)• It takes place in the mitochondrial matrix

– 3. The electron transport system (ETS) = respiratory chain• It’s the second part of aerobic metabolism (cellular respiration)• It takes place at the inner mitochondrial membrane

• #2 and #3 require O2

MP

Gly

coly

sis

MP

Note: the phosphory-lation of glucose to glucose-6-phosphate trapsglucose inside cells (it’s no longer just glucose, so it can’t bind to glucose transporters)

Fig. 25-3, p. 920

An overview of glycolysis• This process occurs in the cytoplasm• What goes in:

– 1 glucose (6 carbons)– 2 ATP– 2 NAD+

• What comes out:– 2 pyruvate (3 carbons each)– 4 ATP– 2 NADH + 2 H+

• Net gains:– 2 ATP by substrate-level phosphorylation– 2 pyruvate to send to the citric acid cycle in the

mitochondria if O2 is available– 2 NADH carrying electrons to send to the ETS if O2 is

available

MP

The fate of pyruvate???• 1. If O2 is NOT available to

the mitochondria:– Pyruvate (pyruvic acid) is

reduced to lactic acid– This regenerates NAD+

(via the oxidation of NADH), which allows glycolysis to continue, producing small amounts of ATP (2 per glucose) anaerobically

• 2. If O2 is available to the mitochondria (see the next slide):– Pyruvate (3 carbons) is oxidized by NAD+ to an acetyl

group (2 carbons), with the loss of CO2

– The acetyl group combines with coenzyme A (CoA), forming acetyl-CoA, which links to the citric acid cycle

MP

Fig. 25-4b, p. 922

The citric acid

cycle

MP

Note: 1 “turn” of the cycle per pyruvate = 2 “turns” of the cycle per glucose (since 1 glucose → 2 pyruvate)

(from glycolysis)

NADH

Pyruvate → acetyl group• This reaction links glycolysis with the citric acid

cycle• This reaction takes place in the mitochondrial

matrix• What goes in (for each glucose):

– 2 pyruvate enter the mitochondrion– 2 NAD+ are used to oxidize the pyruvate

• What comes out (for each glucose):– 2 acetyl groups (which will enter the citric acid

cycle)– 2 CO2 are released– 2 NADH (+ 2 H+) that can carry electrons to the

ETS

MP

An overview of the citric acid cycle• These reactions occur in the mitochondrial matrix• What goes in (for each glucose):

– 2 2-carbon acetyl group molecules (shuttled by CoA) = 2 acetyl-coenzyme A (acetyl-CoA)• These join the final 4-carbon intermediate of the citric acid cycle

(oxaloacetic acid) to produce the first 6-carbon intermediate (citric acid)

– 6 NAD+

– 2 FAD– 2 ADP + GDP + Pi

• What comes out (for each glucose):– 4 CO2

– 6 NADH + 6 H+ (carrying electrons to the ETS)– 2 FADH2 (carrying electrons to the ETS)– 2 ATP (by substrate-level phosphorylation)

MP

The electron transport system (ETS) and oxidative phosphorylation

MP

Fig. 25-5b, p. 924

MP

Fig. 25-5a, p. 924

An ETS electron/energy flowchart

An overview of the ETS (part 1)• These reactions occur at the inner mitochondrial membrane• Electrons carried by NADH or FADH2 are at a very high

energy level (highly reduced) compared to those of oxygen (O).

• The electrons are passed from NADH or FADH2 to other electron carriers (more coenzymes) that are located in or on the inner mitochondrial membrane. The electrons are passed from higher energy carriers to lower energy carriers, and finally down to oxygen (O). This releases energy (that was originally stored in the covalent bonds of nutrients) in small increments rather than in a large blast that would cause you to explode. ☺– At the end of the chain, the reduced oxygen (O) has 2 extra electrons,

so it combines with 2 H+ to form H2O (= metabolic water)• Essentially: 2 H2 + O2 → 2 H20

MP

An overview of ETS (part 2)• The energy released by the cascading of electrons along the

chain is used to actively pump pairs of H+ from the mitochondrial matrix into the intermembrane space. This produces both concentration and electrical gradients that make H+ “want” to diffuse back into the matrix.

• On average, the energy released by electrons from each NADH cause 3 pairs of H+ to be pumped through the inner membrane. 2 pairs of H+ are pumped for each FADH2.

• H+ diffuse across the inner membrane back into the matrix only through a special membrane channel called ATP synthase. This diffusion also releases energy ([high] → [low]). The released energy is used by ATP synthase to drive this reaction: ADP + Pi → ATP.

• On average it takes one pair of H+ to make one ATP– Therefore,

• For each NADH + H+, 3 ATP are produced• For each FADH2, 2 ATP are produced

MP

Fig. 25-6, p. 926

An energy yield summary

CYTOPLASM

MP

Fig. 25-11, p. 937

CYTOPLASM

MP

Where lipids and proteins

can join in

Where lipids and proteins can join inLipids

• Triglycerides → glycerol + fatty acids– Glycerol enters glycolysis– Fatty acids undergo β-oxidation and enter as acetyl-CoA

Proteins• Amino acids enter as:

– Pyruvate– Acetyl-CoA– Citric acid cycle intermediates (e.g. α-ketoglutaric acid)

• Amino acids must be deaminated first, which…– Produces ammonium ions (NH4

+), which…• Are converted by the liver to urea (which is less toxic)

Also: the liver can interconvert among amino acids, fatty acids, and glucose

MP

Nutrients• = substances obtained from the diet that are:

– A. Used to generate energy for energy-requiring processes, such as…

• DNA and protein synthesis• Active transport• Muscle contraction, etc.

– B. Used as building blocks for synthetic processes• E.g. amino acids → proteins

– C. Stored for future use for A and B above• Glucose is stored as glycogen• Triglycerides are stored as fat (adipose)

• Classes of nutrients:– 1. Carbohydrates: polysaccharides (complex carbohydrates) →

monosaccharides (simple sugars)– 2. Fats (lipids): triglycerides → fatty acids + glycerol– 3. Proteins → amino acids– 4. Minerals (see the next slide)– 5. Vitamins (see the next slide after that)– 6. Water

KNOW

Minerals• = inorganic ions needed by the body

– In the body, they are most highly concentrated in the bones

• Some functions:– 1. Structural building blocks (e.g. calcium in bones)– 2. Catalysts (e.g. magnesium is a catalyst for the reaction

ADP + Pi → ATP)– 3. Cofactors (e.g. copper and iron are used in the ETS)– 4. Oxygen carriers (iron in hemoglobin)– 5. Contributors to osmotic concentration in fluids (e.g.

sodium, chloride, and potassium) – 6. Contributors to membrane potentials (e.g. sodium and

potassium)– 7. Muscle contraction (calcium)– And much, much more!

KNOW

VitaminsKNOW

• = organic molecules needed by the body for metabolic functions (usually as coenzymes)

• Are not broken down for energy or used as structural building blocks

• Most cannot be synthesized, and must be absorbed from the diet– Some are synthesized from ingested provitamins

• E.g. vitamin A is synthesized from beta-carotene• Fat-soluble vitamins (= A, D, E, K):

– Are absorbed via micelles with dietary lipids from the GI tract

– Can be stored, especially by hepatocytes• Water-soluble vitamins (= all the rest):

– Are absorbed from the GI tract directly– Most are not stored to any extent

• Excessive amounts are excreted in the urine

Regulation of food intake• These hypothalamic nuclei (centers) are important:

– The feeding (hunger) center – when stimulated, it causes feeding behaviors

• Apparently it is constantly active, but it is inhibited by…– The satiety center – when stimulated, it leads to the cessation of

feeding • A couple of theories:

– The glucostatic theory:• Hypoglycemia decreases the firing rate of satiety center neurons

– This excites the feeding center– The lipostatic theory:

• Some substances (e.g., fatty acids and leptin) that are released from adipose tissue activate satiety center neurons

– This inhibits the feeding center• Other factors:

– A. Ambient temperature (cold → increased feeding)– B. The distension of the GI tract reflexively activates the satiety center– C. Other hormones such as CCK (↑ satiety) and ghrelin (↑ hunger)– D. Psychological factors (e.g. anorexia and bulimia)

KNOW

The basal metabolic rate (BMR)KNOW

• = the overall rate at which energy is expended (and heat is produced) by the body in a human who is:– Quiet– Resting– Fasting– At a thermoneutral ambient temperature

• Is most conveniently measured/estimated via indirect calorimetry:– O2 uptake (or CO2 production) is measured, and that value is put into

a formula to estimate energy expenditure• Male average BMR: 1600-1800 Calories per day• Female average BMR: 1300-1500 Calories per day

• Note that there is much more energy per gram of lipids than per gram of other organic macromolecules:– Lipids yield ~ 9 Calories per gram– Proteins yield ~ 4 Calories per gram– Carbohydrates yield ~ 4 Calories per gram

Some factors that influence BMRKNOW

• 1. Exercise: ↑ BMR• 2. Hormones: e.g. thyroxine and testosterone ↑

BMR • 3. Nervous input: sympathetic stimulation ↑ BMR• 4. Increased body temperature: ↑ BMR• 5. Ingestion of food: ↑ BMR • 6. Age: ↓ BMR• 7. Gender: BMR is lower in females except during

pregnancy and lactation• 8. Diurnal fluctuation: BMR is lower during sleep

(when body temperature is lower)

Body temperature regulation• 1. We maintain a relatively constant core

temperature of about 37°C (98.6°F), but the actual value varies with the time of day, exercise, etc.

• 2. The surface of the body (or shell) is cooler– This allows for the dissipation of metabolically produced

heat that is generated from deeper tissues• The preoptic area of the anterior hypothalamus is the

thermoregulatory control center of the body– It responds to changes in brain temperature– It receives input from peripheral (shell) and central (core)

thermoreceptors– It compares the input to an “optimal” preset temperature– It sends output to effector organs (what are some

examples?)

KNOW

Some specific mechanisms of heat gain

(conservation/retention or generation/production)• If the hypothalamus receives input that body temperature is

falling or is likely to do so, it will initiate…– 1. Behavioral responses, such as…

• Seeking out a warm environment or putting on clothes– 2. Vasoconstriction of peripheral blood vessels

• Especially superficial veins (see the next slide)• This will ↓ heat loss

– 3. Shivering = brief oscillatory contractions of antagonistic muscles• As the muscles generate the ATP needed for this activity, the heat

produced warms the blood in the deeper vessels– 4. Sympathetic stimulation (via the release of NE and E)

• This will ↑ metabolic rate, and thus ↑ heat production– 5. ↑ Thyroid hormone release in a cold environment

• This will ↑ metabolic rate, and thus ↑ heat production

KNOW

Fig. 25-15, p. 946

Sup

erfic

ial v

enoc

onst

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exc

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KNOW

Some specific mechanisms of heat loss

• 1. Behavioral responses, such as…– Seeking a cooler environment or taking off clothes

• 2. Vasodilation of peripheral blood vessels– This will ↑ heat loss to the environment

• 3. Sweat– See “evaporation” on the next slide– Other animals pant or spread saliva

Note that behavioral responses are often activated first

KNOW

General mechanisms of heat transfer/exchange

• 1. Radiation– = the transfer of infrared radiation (heat) from warmer to

cooler objects that are not in physical contact• E.g. heat from a camp fire

• 2. Conduction– = the transfer of heat from warmer to cooler objects that

are in physical contact• 3. Convection

– = the transfer of heat between an object and a moving, fluid medium like air or water

• 4. Evaporation– = the conversion of liquid water into water vapor (gas),

which requires a lot of heat energy• Sweating thus removes heat from the body when it evaporates

KNOW